4
40 | NewScientist | 7 July 2007 www.newscientist.com IN JULY 2005, a 23-year-old British woman was involved in a horrific road accident. She was taken to hospital in a deep coma with a serious head injury. After an operation to relieve the pressure on her brain, she gradually woke up, but only to what’s been called a “living death” – a condition known as a persistent vegetative state. PVS is an unnerving name and equally disturbing to witness. The patient is clearly alive, breathing unaided, but the person who was once there seems to have gone. They sleep and wake and move, though their movements are erratic. They may speak or make noises, even smile, cry or grimace, but they seem to do nothing of their own free will. They respond to neither pain nor stimulation. What if thousands of people who seem to be locked in a persistent vegetative state are actually aware of their predicament? Helen Phillips investigates. Throughout their 19-year vigil, Terry Wallis’s family insisted he was still there, and they were right Impossible awak It was a shock, then, when neuroscientists examining the woman – let’s call her patient X – claimed to have detected unmistakable flickers of consciousness during a brain scan. If they were right, although she met the hospital’s clinical criteria for PVS – most importantly, wakefulness but total lack of awareness in a standardised bedside test – she was not entirely unconscious. The discovery is just one of several recent cases that seem to defy medical understanding. As well as unexpected flickers of awareness there have been seemingly impossible “awakenings”, such as the case of Terry Wallis, who suddenly came round 19 years after he became unconscious. There are also growing numbers of reports of drugs that can rouse otherwise unresponsive patients. PVS and other disorders of consciousness (see Diagram, page 42) have long been among the most medically and ethically challenging conditions, but this has turned them into a minefield. What do these awakenings mean for the hundreds of thousands of patients diagnosed with PVS and other disorders of consciousness? Could some of them be aware of their predicament, trapped inside a body they can no longer control? Can standard tests distinguish between those who are still “in there” and those who are truly unaware and unlikely ever to recover? Are patients who have a chance of waking up being allowed to die because doctors assume they have no future (see “A right to die?” page 42)? DANNY JOHNSTON/AP BRIAN CHILSON/AP

Impossible awakenings

Embed Size (px)

Citation preview

Page 1: Impossible awakenings

40 | NewScientist | 7 July 2007 www.newscientist.com

● IN JULY 2005, a 23-year-old British

woman was involved in a horrific road

accident. She was taken to hospital in a

deep coma with a serious head injury. After an

operation to relieve the pressure on her brain,

she gradually woke up, but only to what’s been

called a “living death” – a condition known as a

persistent vegetative state.

PVS is an unnerving name and equally

disturbing to witness. The patient is clearly

alive, breathing unaided, but the person who

was once there seems to have gone. They sleep

and wake and move, though their movements

are erratic. They may speak or make noises,

even smile, cry or grimace, but they seem to

do nothing of their own free will. They

respond to neither pain nor stimulation.

What if thousands of people who seem to be lockedin a persistent vegetative state are actually aware of their predicament? Helen Phillips investigates.

Throughout their 19-year vigil, Terry Wallis’s family insisted he was still there, and they were right

Impossible awakeIt was a shock, then, when neuroscientists

examining the woman – let’s call her patient

X – claimed to have detected unmistakable

flickers of consciousness during a brain scan.

If they were right, although she met the

hospital’s clinical criteria for PVS – most

importantly, wakefulness but total lack of

awareness in a standardised bedside test –

she was not entirely unconscious.

The discovery is just one of several recent

cases that seem to defy medical understanding.

As well as unexpected flickers of awareness

there have been seemingly impossible

“awakenings”, such as the case of Terry Wallis,

who suddenly came round 19 years after he

became unconscious. There are also growing

numbers of reports of drugs that can rouse

otherwise unresponsive patients. PVS and

other disorders of consciousness (see Diagram,

page 42) have long been among the most

medically and ethically challenging conditions,

but this has turned them into a minefield.

What do these awakenings mean for the

hundreds of thousands of patients diagnosed

with PVS and other disorders of

consciousness? Could some of them be aware

of their predicament, trapped inside a body

they can no longer control? Can standard

tests distinguish between those who are still

“in there” and those who are truly unaware

and unlikely ever to recover? Are patients

who have a chance of waking up being allowed

to die because doctors assume they have

no future (see “A right to die?” page 42)?

DANN

Y JOH

NSTO

N/AP

BRIA

N CH

ILSO

N/AP

070707_F_PVS.indd 40070707_F_PVS.indd 40 29/6/07 4:01:30 pm29/6/07 4:01:30 pm

Page 2: Impossible awakenings

Most cases of PVS come about as a patient

claws their way out of a coma after a head

injury, or after their brain has been deprived

of oxygen in a heart attack or stroke. The early

stages are defined simply as a “vegetative

state”, and many patients pass through this

on their way to some form of recovery. Those

who languish for longer than 30 days are

generally diagnosed with PVS – though

“persistent” doesn’t necessary mean

permanent, and a handful of patients regain

consciousness months later. After a year

following brain injury, or three to six months

after a stroke or heart attack, the chances of

recovery are slim, and the patient is often

declared to be in a permanent vegetative state.

PVS has always been difficult to diagnose

www.newscientist.com 7 July 2007 | NewScientist | 41

and manage largely because it is not so much a

diagnosis as a symptom, and no single brain

region or function is lost. (For typical diagnostic

criteria, as used in the UK, see Clinical Medicine,

vol 3, p 250 .) It is also incredibly hard to predict

an individual patient’s chances of recovery.

So do the recent events really change the

picture, and if so, how?

The team who studied patient X now have

more clues as to what their discovery might

mean. PVS patients often have reflex-like

responses in the brain to words, sounds, faces

and painful stimuli, but these register only in

the outermost sensory areas and never reach

regions that might become aware of them.

What Adrian Owen from the Medical Research

Council Cognition and Brain Sciences Unit

in Cambridge, UK, and colleagues at the

University of Cambridge and University

of Liège in Belgium wondered was whether

patient X’s response could be more

sophisticated than that. Could she respond

to instructions to perform a mental task that

a brain scanner could pick up?

Normally just thinking about actions

produces similar patterns of brain activation

to actually performing them. So Owen and his

colleagues picked two actions involving very

different brain regions: walking around your

home, which uses spatial awareness and

memory regions; and playing tennis, which

uses regions that control limb movement.

Having established that functional MRI could

identify these thought patterns in normal

kenings

Every morning, Louis Viljoen is given a drug that somehow reverses his PVS for a few hours

ALEX

IA W

EBST

ER/T

HE SU

NDAY

TELE

GRAP

H

070707_F_PVS.indd 41070707_F_PVS.indd 41 29/6/07 4:01:55 pm29/6/07 4:01:55 pm

Page 3: Impossible awakenings

might have run a little differently if routine

scanning had been available. In 1984, at the

age of 19, he was thrown from his pick-up truck

near his home in Massachusetts, and was

found in a coma the next day. A few weeks later,

he was diagnosed with PVS and released into

family care. He didn’t see a neurologist again

for 19 years. His mother always maintained

that there was something of Terry still inside,

and apparently she was right. In 2003, she was

rewarded when Wallis uttered his first word

since the accident: “Mom”. Over the next

three days, he regained the ability to move

and communicate a little, and had the shock

of coming to terms with the fact that it was

no longer 1984, he was no longer a teenager,

and that his baby daughter was now 20.

To find out more about Wallis’s apparently

miraculous recovery – the latest awakening

on record – neurologist Nicholas Schiff from

the Weill Medical College of Cornell University

in New York twice scanned Wallis’s brain using

diffusion tensor imaging. This technique

reveals the connectivity patterns in the brain

rather than just anatomy or activity. The scans

showed that while his brain structure was

relatively intact the connections between

regions, especially those between the two

hemispheres, were torn apart.

Comparing scans from eight months and

26 months after his awakening, Schiff found

some clues as to why Wallis may have

resurfaced. The normal connections between

the hemispheres were much less substantial

than usual – “like a small wispy string”, says

Schiff. But a completely novel structure had

developed towards the back of his brain and

was showing strong connectivity between

the two hemispheres (Journal of Clinical Investigation, vol 116, p 2005) . Developing this

new structure was clearly a very long and slow

process that could well have taken 19 years.

If it can take two decades for the brain

to recover, just how persistent is PVS, and

how long might unconsciousness last? How

might doctors decide which patients warrant

a lengthy vigil, and make sure that families

seeking the right to die for their loved ones

are not denying them a late awakening?

It’s hard to say. When Schiff studied the

case notes, he found that Wallis had not been

in a vegetative state after all. His diagnosis,

certainly from around three months after

the accident, fitted better with the minimally

conscious state. Schiff argues that nobody

properly diagnosed as being in a PVS has ever

experienced a late recovery.

Even if Wallis wasn’t in a PVS, his late

awakening from minimal consciousness

is still baffling. And there are other, similar

cases that defy medical understanding. Take

49-year-old Christa Lilly from Colorado, who

suffered a stroke and heart attack in 2000 and

and Owen says she has shown some signs

of improvement. She is now considered

to be in a “ minimally conscious state ”, a

recently defined category which allows for

sporadic signs of awareness and attempts

to communicate. It seems likely that her

early signs of awareness reflected the first

stirrings of recovery.

It therefore seems unlikely that legions

of PVS patients are suffering in silence, aware

of their predicament but unable to

communicate. It may simply be that brain

scanning is capable of picking up signs of

recovery earlier than clinical tests, Owen

says. He thinks it won’t be long before brain

imaging becomes a standard diagnostic tool.

Terry Wallis is one person whose story

volunteers, they asked patient X either

to imagine playing tennis or to imagine

walking around her house. Sure enough, they

found that she showed the same distinctive

patterns of brain activity (Science, vol 313,

p 1402). Owen believes this can only

mean one thing: “This patient was consciously

aware and purposefully following the

instructions given to her, despite her

diagnosis of vegetative state.”

In subsequent tests of around a dozen

patients the team has found only one other

who responds to instructions in a similar

way. So patient X’s condition looks like a

rarity, though by no means a one-off.

What does this mean for other PVS

patients? Patient X is still under observation,

42 | NewScientist | 7 July 2007 www.newscientist.com

A right to die?Late awakenings from apparently

persistent vegetative states have created

concern about decisions to allow some

patients to die on the basis that they

have no hope of recovery. Should the

right to die still exist?

The right to die was hard-won,

established in law in the US in 1976 and

in UK case law in 1993. Right-to-die cases

now only go to court if doctors or family

members disagree.

So far all right-to-die decisions

have been supported by autopsy results.

Yet even where there is unequivocal

evidence that PVS is irreversible, the

right to die can be controversial, as

in the case of Terri Schiavo in 2005.

She had been in a PVS for 15 years and

had shown no signs of recovery.

Yet the White House and the Vatican got

involved, and Schiavo’s feeding tube

was removed and reinserted four times

before she was allowed to die.

Recent discoveries are having an

effect. In one case a UK judge issued

an order to try zolpidem on a PVS

patient against her family’s wishes,

before considering the right to die.

Researchers generally agree that

the right to die should remain an

option, and that a correct diagnosis of

PVS usually goes along with irreversible

neural death. The problem, it seems,

is not with the right itself, or even

challenging the persistence of true

PVS, but with recognising patients

who might instead be in the twilight

of the minimally conscious state.

070707_F_PVS.indd 42070707_F_PVS.indd 42 29/6/07 4:02:15 pm29/6/07 4:02:15 pm

Page 4: Impossible awakenings

Terri Schiavo (left) was allowed to die; Christa Lilly (above) awoke after several years, but later relapsed

CARL

OS B

ARRI

A/RE

UTER

S

www.newscientist.com 7 July 2007 | NewScientist | 43

which seems to have had some success.

Drugs may not be the only treatment

option. Deep brain stimulation (DBS), using

implanted electrodes that work a bit like a

pacemaker for the brain, has shown some

promise. On the basis of one small trial,

researchers at Nihon University School of

Medicine in Japan claim that PVS patients

who receive DBS are more likely to regain

consciousness than those who don’t. Using

a slightly different technique, Schiff has

found that DBS can produce brain activity

rather like wakeful arousal, though not actual

awakening. He is planning a bigger trial on

patients in the minimally conscious state.

Even low-tech options such as physical

rehab are producing results. The Leijpark

Rehabilitation Centre in Tilburg, the

Netherlands, is a model of how effective it

can be. The centre places great importance

on daily routine, with separate living rooms

and bedrooms, for example. Patients sit up

and are given physiotherapy and sensory

stimulation up to three times a day.

Treatment does not come cheap – upwards

of €1000 a day – but it does seem to pay off.

Although the centre has not done formal

clinical trials, it claims about twice as many

of its patients regain consciousness compared

with published averages – though the odds

may be stacked in its favour as its patients

are all children or young adults and are often

at the most favourable end of the spectrum.

Unfortunately, Leijpark is a rarity.

Physiotherapy is expensive and is generally

seen as unnecessary for patients who are not

expected to wake up.

Joseph Fins, who heads the division of

medical ethics at Weill, says that patients

in minimal consciousness are among the

most neglected of all patients in long-term

care. “We spend hundreds of thousands

of dollars saving their lives, then we let

them linger in suboptimal care,” he says.

“They have no rehab and no supportive

care. If their brains recover, their bodies have

deteriorated.” Schiff agrees that the care of

brain-injured patients is “a disaster”.

As knowledge about disorders of

consciousness improves, however, the

prospects for patients can only get better.

The US Institute of Medicine recently

convened a meeting of researchers, ethicists,

legal experts and policy-makers to discuss

the implications of the recent developments .

All agreed that improving treatment and

research into disorders of consciousness is

an urgent priority. They described a “silent

epidemic” of brain-injured patients who are

being neglected for want of medical care – and

research. For those in search of a miracle, the

odds are still long. But awareness at last seems

to be rising, in more ways than one. ●

“Louis’ mother was there the first time he woke up”lies unconscious in what was originally

diagnosed as PVS, except for three days earlier

this year and another five occasions

beforehand when she has woken up and

picked up where she left off. Her doctors now

consider her to be minimally conscious, but

do not know why she slips in and out of this

state. In January, a 44-year-old man in Italy

awoke 19 months after a brain haemorrhage,

even though recovery from this type of injury

is usually considered impossible after three

months. And last month a Polish rail worker,

Jan Grzebski, woke from what media reports

called a 19-year coma, though chances are he

actually had locked-in syndrome, in which the

patient is aware but completely paralysed.

Sleeping pill paradoxEven more astonishing is the case of Louis

Viljoen , who lives in a rehabilitation centre

near Johannesburg, South Africa. Every

morning he wakes up from his PVS, enjoys

a period of alertness and then lapses back

into unconsciousness. His secret is a sleeping

pill called zolpidem, which paradoxically

seems to rouse him.

In 1996, when he was 25, Viljoen was hit

by a truck while riding his bike. Initially his

brain injuries left him in a coma, but gradually

he settled into what his doctors called PVS.

In 1999 his doctor, Wally Nell, prescribed him

zolpidem in an attempt to stop him harming

himself as he thrashed about in bed.

His mother was there the first time

he received the drug. She was also there to

witness his miraculous first words less than

half an hour later. Though he was blind, he

could recognise his mother’s voice. His daily

dose of zolpidem now gives him roughly

10 hours of alertness. He remembers his

previous awakenings and has retained his

sense of humour. He is still blind, and has

short-term memory problems, but his mental

functions are improving all the time.

Nell has since tried zolpidem on around

200 people with various brain injuries and

claims that around half show some benefit,

though very few were as seriously injured as

Viljoen. However, other institutions, including

Schiff’s, have had nowhere near such high

success rates. Some suggest that the successes

may not have been true cases of PVS, but

something more like minimal consciousness.

Either way, neuroscientists are now studying

the zolpidem effect and several clinical trials

are getting under way. The first results should

be in later in the year.

Zolpidem is not the only promising drug.

Others have shown success in informal trials,

including antidepressants, Parkinson’s drugs

such as L-dopa, and stimulants such as ritalin.

John Whyte of the Moss Rehabilitation

Research Institute in Philadelphia,

Pennsylvania, says it is high time that these

anecdotal treatments were tested more

rigorously, though he cautions that doing so

is difficult. Because PVS is a long-term

condition and varies from patient to patient,

huge groups are needed to get significant

results. What’s more, families that enrol in

trials need to accept the possibility that their

loved one will be given a placebo rather than

the drug itself. Whyte himself is in the process

of recruiting 180 PVS patients for a clinical

trial for amantadine, a Parkinson’s drug

KKTV

-TV/

AP

070707_F_PVS.indd 43070707_F_PVS.indd 43 29/6/07 4:02:29 pm29/6/07 4:02:29 pm